General

Scientific Names: Coriolus versicolor, Trametes versicolor.

Common Names: Yun Zhi , Turkey Tail.

BOTANICAL:

Coriolus versicolor (CV), also known as Yun Zhi, is a mushroom used in traditional Asian herbal remedies (see Chinese Herbal medicine). A protein-bound polysaccharide K (PSK) from the mushroom, is being studied as a possible cancer treatment. A polysaccharide is a starch-like carbohydrate formed by a large number of sugar molecules.

Mushrooms have traditionally been valued in Asia for their nutritional and medicinal qualities. The CV has been investigated in numerous laboratory, animal, and human clinical studies. Most of these studies have demonstrated that it does appear to have significant antimicrobial, antiviral, and antitumor properties when used as a supplement to chemotherapy and/or radiotherapy. The anti-cancer and immune stimulating properties of Coriolus versicolor have been attributed to two extracts from its cultured mycelium (immature form with thread-like extensions). These extracts are both protein-bound polysaccharides known as Polysaccharide K (PSK) and Polysaccharide-Peptide (PSP). Hot water is required to extract these active components. There is scientific evidence from clinical trials which suggests that PSK and PSP may provide benefit to people with cancer, including increased survival rates and longer disease-free periods, without causing significant side effects.

• 性状鉴别：子实体无柄。菌盖扇形、半圆形或贝壳形。常数个叠生成覆瓦状或莲座状，直径1-10cm，厚1-4mm，表面密生灰、褐、蓝、紫、黑等颜色的绒毛，并构成多色的狭窄同心性环带，边缘薄，全缘或波状，管口面灰褐色、黄棕色或浅黄色，管口类圆形或多角形，部分管口齿裂，每 1mm 间 3-5 个。革质，不易折断。气微，味淡。

• 显微鉴别：本品纵切面置解剖镜下观察，皮壳外侧为绒毛层，为长短不等的菌丝，菌丝不分枝；皮壳菌丝排列紧密，菌丝胞腔含有众多色素颗粒。菌肉层厚，无色，菌丝紧密排列。最下方为菌管层，菌管排列整齐。

• 粉末特征： 3.1．孢子圆筒形，稍弯曲，大小不匀，长 5-7μm，直径 2-3μm，外壁平滑，无色，内壁浅褐色。 3.2．绒毛菌丝无色，单个或数个相连，不分枝，直径3-5μm，壁上有多枝颗粒状物质。 3.3．骨架菌丝较粗， 直径 5-7μm， 不分枝，壁较平直，无色。 3.4．生殖菌丝直径 3-4μm，不分枝，壁平直、极薄、透明。 3.5．缠绕菌丝较细，直径 1.5-4 μ m，常弯曲。

• 理化鉴别：取本品粗粉 2g ，加水 20ml ，水浴加热 10 分钟，滤过，取滤液 2ml ，加碱性酒石酸铜试液 4-5 滴，水浴上加热 5 分钟，生成红色沉淀。

Proponents claim that PSK and PSP, the active ingredients in CV, have strong anti-cancer properties. Literatures also say that PSK and PSP have antimicrobial and antiviral properties and that it stimulates cells in the blood that destroy invading microorganisms.

  1. Monro JA. Treatment of cancer with mushroom products. Arch Environ Health. 2003 Aug.
  2. Cui J, et al., Polysaccharopeptides of Coriolus versicolor: physiological activity, uses, and production. Biotechnol Adv. 2003 Apr.
  3. Kidd PM, The use of mushroom glucans and proteoglycans in cancer treatment . Altern Med Rev. 2000 Feb.
  4. Ng TB, A review of research on the protein-bound polysaccharide (polysaccharopeptide, PSP from the mushroom coriolus versicolor (Basidiomycetes: Polyporaceae). Gen Pharmacol. 1998 Jan.
  5. Tsukagoshi S, et al., Krestin (PSK). Cancer Treat Rev. 1984 Jun.

 

Pharmacology

Using the differential display reverse-transcriptional polymerase chain reaction (DDRT-PCR) technique, several cDNA fragments were isolated as chemical stress responsive genes from the white-rot basidiomycete, Coriolus versicolor, exposed to either 4-methyldibenzothiophene-5-oxide (4MDBTO) or dibenzothiophene-5-oxide (DBTO). A database search on deduced amino acid sequences of cDNAs revealed that they showed a high similarity with various proteins from other organisms. These results strongly suggested that cell responding systems might be involved in the fungal metabolism of exogenous chemicals by C. versicolor. One of the significantly up-regulated cDNA fragments by MDBTO, DD16gc, showed a high similarity to arylalcohol dehydrogenases (AADs) from several microorganisms. The full-length cDNA sequence of the DD16gc determined by 5' rapid amplification of cDNA ends method revealed that the gene consisted 1,295 nucleotide and poly(A) tail, encoding 394 amino acids in an open reading frame. The deduced protein showed a remarkable homology to AAD from Phanerochaete chrysosporium (66% identity) and to that from Saccharomyces cerevisiae (54% identity). The AAD gene was specifically transcripted under chemically-stressed conditions by 4MDBTO, suggesting that the enzyme encoded by the stress responsive gene may play an important role in the fungal conversion of 4MDBTO or its metabolic product(s). (Source)

云芝菌体多糖对小鼠腹腔巨噬细胞可加强其吞噬作用，对环磷酰胺引起的脾脏萎缩具有对抗作用。云芝菌体多糖及滤液多糖能使胸腺缩小、脾重增加。有人认为和文献报道的短小棒状杆菌的作用颇相类似。国产云芝胞内多糖明显增加网状内皮细胞的吞噬活性，明显增加小鼠对金黄色葡萄球菌、大肠杆菌、宋氏痢疾杆菌及绿脓杆菌感染的非特异性抵抗力。云芝多糖肽（PSP） 100-800 μ g/ml 能使淋巴细胞明显增殖，小鼠腹腔内注射环磷酰胺 25mg/kg 抑制活化 T 细胞产生白介素 2 （IL-2）和 T 细胞中介的迟发型超敏反应（DTH），如同时给予 PSP 25mg/kg ，连续 5 天，可对抗上述免疫抑制效应。 PSP10-100 μ g/ml 浓度时可使人外周白细胞产生α - 和γ - 干扰素（IFN）的能力较对照组提高 8 倍和 4 倍。此外， PSP 还能增强网状内皮系统的吞噬功能。云芝多糖（PSK）对用 60Co 200 γ全身一次照射，造成小鼠免疫功能低下，具有一定的治疗作用。能明显增加被照射小鼠血清溶菌酶含量和脾指数，认为对巨噬细胞的非特异性免疫功能具有促进作用。干扰素诱生和促诱生的试验结果表明，云芝多糖肽的抗肿瘤和免疫调节作用可能与它具有干扰素诱生和促诱生能力有关。大鼠连续口服云芝多糖肽 20g/kg/ 天可促进淋巴细胞转化，血清 IgG 滴度明显升高，还可取消大鼠隔日服环磷酰胺 400mg/kg 对自然杀伤细胞功能的抑制。用化学发光法观察到，云芝多糖经腹腔注射后，能增强小鼠腹腔巨噬细胞呼吸爆发功能对叔丁基氢过氧化物损伤的抵抗力。云芝多糖处理的巨噬细胞谷胱甘肽过氧化物酶（GSHPx）基础活力显著提高，在叔丁基氢过氧化物作用下，云芝多糖处理的巨噬细胞仍有较高的谷胱甘肽过氧化物酶活力。说明云芝多糖作为免疫刺激剂具有能提高抗氧化酶活力，保护巨噬细胞抵抗活性氧损伤的作用。服用云芝多糖的恶性肿瘤患者，其 T3 、 T4 淋巴细胞亚群及白细胞计数，均较眼药前显著增加，认为是一种较好的生物反应调节剂。云芝多糖对受氧化低密度脂蛋白（O-LDL）损害小鼠巨噬细胞造成的脂肪堆积，有保护作用，并能抑制巨噬细胞泡沫样变性，提高巨噬细胞反应能力。对环磷酰胺造成的小鼠白细胞减少有明显的回升作用，能激活网状内皮系统的功能。可显著提高脾细胞产生的 IL-2 、淋巴毒素和γ - 干扰素的水平，显著增强腹腔巨噬细胞分泌肿瘤坏死因子和 IL-1 的能力。

  1. Lin JP, et al., Production of laccase by Coriolus versicolor and its application in decoriztion of dyestuffs: (I.) Production of laccase by batch and repeated-batch processes. J Environ Sci (China), 2003 Jan.
  2. Lin Jp, et al., Production of laccase by Coriolus versicolor and its application in decoriztion of dyestuffs: (II) Decolorization of dyes by laccase containing fermentation broth with or without self-immobilized mycelia. J Environ Sci (China), 2003 Jan.
  3. Ichinose H, et al., Molecular analysis of arylalcohol dehydrogenase of Coriolus versicolor expressed against exogenous addition of dibenzothiophene derivatives. J Basic Microbiol. 2002.
  4. Mau Jl, et al., Antioxidant properties of several medicinal mushrooms. J Agric Food Chem. 2002 Oct 9.
  5. Limura Y, et al., Structure of genes for Hsp30 from the white-rot fungus Coriolus versicolor and the increase of their expression by heat shock and exposure to a hazardous chemical. Biosci Biotechnol Biochem, 2002 July.
  6. Morita Y, et al., Biological activity of 4-acetyltropolone, the minor componer of Thujopsis dolabrata Sieb. Et Zucc. Hondai Mak. Biol Pharm Bull, 2002 Aug.
  7. Ichinose H, et al., Identification and characterization of novel cytochrome P450 genes from the white-rot basidiomycete, Coriolus versicolor . Appl Microbiol Biotechnol, 2002 Jan.
  8. Hiratsuka N, et al., Degradation of diphenyl ether herbicides by the lignindegrading basidiomycete Coriolus versicolor. Appl Microbiol Biotechnol. 2001 Nov.
  9. Leontievsky AA, et al., Transformation of 2, 4, 6,-trichlorophenol by free and immobilized fungal laccase. Appl Microbiol Biotechnol. 2001 Oct.
  10. Lan J, et al., Resources and utilization of anticarciogenic medical fungi . Zhong Yao Cai. 1999 Dec.
  11. Nakamura K, et al., Susceptibility of natural killer (NK) cells to reactive oxygen species (ROS) and their restoration by the mimics of superoxide dismutase (SOD). Cancer Biother Radiopharm. 1998 Aug.
  12. Wei WS, et al., Effects of Coriolus versicolor polysaccharides on superoxide dismutase activities in mice. Zhongguo Yao Li Xue Bao. 1996 Mar.
  13. Kobayashi Y, et al., Suppressive effects on cancer cell proliferation of the enhancement of superoxide dismutase (SOD) activity associated with the protein-bound polysaccharide of Coriolus versicolor QUEL. Cancer Biother. 1994 Summer.

 

Efficacy

Cancer has been attributed to 3 causes: pollution, infection, and poor nutrition. Conventional treatments include surgery, chemotherapy, and radiotherapy. It is proposed that immunotherapy also be considered. Among other environmental influences, dietary deficiencies and carcinogenic viral infections must be investigated and treated wherever possible. It has been suggested that mushrooms, in particular, have a structure that is immunomodulatory because it resembles the proteoglycan structure in the human extracellular matrix, and both are metabolically active. Inasmuch as mitochondria have a bacterial origin, proteoglycans may have a mushroom origin. Studies show that natural killer cells can double in number with 8 wk of treatment with Coriolus versicolor. Also described is an epidemiological survey of cancer deaths among Flammulina velutipes farmers in Japan, which found that the mushroom farmers had lower rates of cancer deaths than controls who were not involved in mushroom farming.

Although recent studies have demonstrated CV's antitumour activities on cancer cells in vitro and in vivo, the exact mechanism is not fully elucidated. Hence, the objective of one study was to examine the in vitro cytotoxic activities of a standardized aqueous ethanol extract prepared from CV on a B-cell lymphoma (Raji) and two human promyelocytic leukemia (HL-60, NB-4) cell lines using a MTT cytotoxicity assay, and to test whether the mechanism involves induction of apoptosis. Cell death ELISA was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis. The results demonstrated that CV extract at 50 to 800 microg/ml dose-dependently suppressed the proliferation of Raji, NB-4, and HL-60 cells by more than 90% (p < 0.01), with ascending order of IC50 values: HL-60 (147.3 +/- 15.2 microg/ml), Raji (253.8 +/- 60.7 microg/ml) and NB-4 (269.3 +/- 12.4 microg/ml). The extract however did not exert any significant cytotoxic effect on normal liver cell line WRL (IC50 > 800 microg/ml) when compared with a chemotherapeutic anticancer drug, mitomycin C (MMC), confirming the tumour-selective cytotoxicity. Nucleosome productions in HL-60, NB-4 and Raji cells were significantly increased by 3.6-, 3.6- and 5.6-fold respectively upon the treatment of CV extract, while no significant nucleosome production was detected in extract-treated WRL cells. The CV extract was found to selectively and dose-dependently inhibit the proliferation of lymphoma and leukemic cells possibly via an apoptosis-dependent pathway.

  1. Ooi VE, et al., Immunomodulation and anti-cancer activity of polysaccharide-protein complexes. Curr Med Chem. 2000 Feb.
  2. Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev. 2000 Feb.
  3. Wang HX, et al., Immunomodulatory and antitumor activities of a polysaccharide-peptide complex from a mycelial culture of Tricholoma sp., a local edible mushroom. Life Sci. 1995.
  4. Kobayashi H, et al., Antimetastatic effects of PSK (Krestin), a protein-bound polysaccharide obtained from basidiomycetes: an overview. Cancer Epidemiol Biomarkers, Prev. 1995 Apr-May.

IN VITRO:

Prevention and cancer control properties of PSK have been associated with its antioxidant and free radical scavenging properties in vitro and in vivo. PSK has demonstrated prevention of chemically induced DNA damage (sister chromatid exchanges) and subsequent tumors due to chemicals, radiation, or other causes.

PSK and PSP also seems to work in multiple steps of the malignant process by inhibiting adhesion, invasion, motility, and metastatic growth of tumor cells in animal models of cancer. Adhesion and invasion are inhibited by suppression of cell matrix-degrading enzyme production by malignant cells. Motility of malignant cells and subsequent attachment to blood vessels are inhibited by suppression of tumor-cell induced platelet aggregation and anti-angiogenic factors.

Immune responsiveness of the host does not appear to be affected by PSK or PSP under normal conditions, but immune systems depressed by tumor-burden or chemotherapy, have reportedly been restored to normal levels by PSK in animal studies. Immune restoration has included antibody and cytokine production, improvement of impaired antitumor activity of natural killer cells, T cells, macrophages, and peripheral blood lymphocytes in vivo and in vitro.

PSK has stimulated differentiation (maturation) of human myeloblastic leukemic cells and suppressed the expression of a heat shock protein involved in the progression of fibrosis.

When injected directly into a tumor, PSK produces local inflammatory responses that result in the non-specific killing of tumor cells.

  1. Lau CB, et al., Cytotoxic activities of Coriolus versicolor (Yunzhi) extract human leukemia and lymphoma cells by induction of apoptosis. Life Sci. 2004 July 2.
  2. Kanazawa M, et al., Effect of PSK on the maturation of dendritic cells derived from human perpheral blood monocytes. Immunol Lett. 2004 Feb.
  3. Tsang KW, et al., Coriolus versicolor polysaccharide peptide slows progression advanced non-small cell lung cancer . Respir Med. 2003 June.
  4. Hsieh TC, et al., Effects of extracts of Coriolus versicolor on cell-cycle progression and expression of interleukins-1 beta, 6, and –8 in promyelocytic HL-60 leukemic cells na imtogenically stimulated and nonstimulated human lymphocytes . J Altern complement Med. 2002 Oct.
  5. Chu KK, et al., Coriolus versicolor: amedicinal mushroom with promising mmunotherapeutic values . J Clin Pharmacol, 2002 Sept.
  6. Fisher M, Yang LX. Anticancer effects and mechanisms of polysaccaride-K (PSK): implication of cancer immunotherapy. Anticancer Res. 2002 May-June.
  7. Mao XW, et al., Evaluation of polysaccaropeptide effects against C6 glioma in combination with radiation , Oncology, 2001.
  8. Liu SL, et al., Inhibition of Proliferation and Expression of N-ras in Hepatoma Cells by Antiocidation Treatment. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), 2001.
  9. Mao XW, et al., Immunotherapy with low-dose interleukin-2 and a polysaccharopeptide derived from Coriolus versicolor. Cancer biother Radiopharm, 1996 Dec.
  10. Ebina T, et al., [Antitumor effect of intratumoral administration of a Coriolus preparation, PSK: inhibition of tumor invasion in vitro]. Gan To Kagaku Ryoho. 1994 Sep.
  11. Anai H, et al., A protein-bound polysaccharide immunomodulator, PSK, does not suppress the conversion from 1-(2-tetrahydrofuryl)-5-fluorouracil to 5-fluorouracil in patients with gastric cancer. Anticancer Drugs. 1991 Jun.
  12. Ebina T, et al., Antitumor effect of PSK at a distant site: inductions of interleukin-8-like factor and macrophage chemotactic factor in murine tumor. Jpn J Cancer Res. 1990 Dec.
  13. Sakagami H, et al., Stimulation of human peripheral blood polymorphonuclear cell iodination by PSK subfractions. Anticancer Res. 1990 May-Jun.
  14. Hsieh TC, et al., Cell growth and gene modulatory activities of Yunzhi (Windsor Wunxi) from mushroom Trametes versicolor in androgen-dependent and androgen-insensitive human prostate cancer cells.
  15. Ito H, et al., Effects of coriolan, an antitumor polysaccharide, produced by Coriolus versicolor Iwade. Jpn J Pharmacol. 1979 Dec.
  16. Kataoka T, et al., Enhanced induction immune resistance by concanavalin A-bound L 1210 vaccine and an immunopotentiator prepared from Coriolus versicolor. Cancer Res. 1977 Dec.
  17. Ito H, et al., [Studies on antitumor activities of Basidiomycetes-antitumor activity of polysaccharides and sex factors]. Nippon Yakurigaku Zasshi. 1976.
    .

 

IN VIVO:

PSP has suppressed the growth of human cancer cell lines in mice (sarcoma 180, lung adenocarcinoma and Lewis lung cancer). It has also inhibited incorporation of two structural units of DNA (uridine and thymidine) in Ehrlich ascites tumor cells, inhibited the growth of P388 leukemia cells, and demonstrated anti-proliferative activity against cell lines of human gastric cancer, lung cancer, lymphoma, and mononuclear leukemia.

PSP has reversed tumor-induced immunodeficiencies in sarcoma-bearing mice by increasing immunoglobulin G and C complement levels. It has also been associated with increases in white blood cell count, serum Ig G, CD, CD8, B-lymphocytes, and neutrophils, along with a higher survival rate of tumor bearing mice. Many of these effects have been attributed to PSP being a strong scavenger of superoxide and hydroxyl radicals.

云芝多糖（PSK）对肉瘤 S180 、白血病 L1210 和腺癌 755 均有抑制作用。肿瘤移植前 10 天给小鼠服用云芝提取物，对小鼠移植后 12 天的腹水型肉瘤 S180 有明显的抑制作用，移植后 22 天抑瘤作用减弱。不同地区的野生云芝提取物进行比较，无论陕西云芝或长白山云芝，对 S180 都有明显的抑瘤作用。云芝菌株在真菌体内积累多糖，还向培养液分泌胞外多糖，前者是葡聚糖，能抑制小鼠 S180 ，并对巨噬细胞有激活作用。后者为多种单糖组成的杂多糖，有一定程度的免疫活化作用，但无明显抑瘤作用。粗制品如云芝菌丝热水提取物，对 S180 抑制率为 77.5% ，精制品活性加大，对 S180 抑制率达 99.3% 。由于 PSK 能明显抑制动物多种肿瘤，抗瘤谱较广，具有一定的临床疗效，故已引起广泛的注意，并已有许多资料证明其抗瘤作用是确定的。 PSK 由于提取方法不同，抑瘤率有所差别，实验表明：氧化还原及部分水解法提取的多糖，抑瘤作用较强。经气化、还原提取的多糖能显著延长生存率。陕西云芝提取物对皮下移植的腹水肝癌小鼠腹腔巨噬细胞没有激发增强作用，吞噬活性较低，但对 S180 ，巨噬细胞受到激活，吞噬功能增强，说明对不同肿瘤可能具有不同的作用。许多研究表明 PSK 提高机体免疫功能和抗肿瘤作用有一定的关系。云芝多糖肽（PSP）可使小鼠血清溶血素、 IgG 、补体 C3 明显提高，对 S180 的抑瘤率为 35%-69% 。抑瘤率比 PSK 低。 PSP1-2g/kg ，连续给药 15-20d. 对裸鼠人肺腺癌有明显的抑制作用，抑制率为 50%-70% ，在抑制肿瘤生长的同时，未见血液和体重变化等毒副反应。从 PSP 粗浸膏中分离到新的小分子肽，相对分子质量 10K 较 PSP （100K）为小，对人的白血病细胞 HL-60 、直肠瘤细胞 LS174-T 、肝癌细胞 SMMU7721 和胃癌细胞 SCG7901 具有强大的细胞毒作用。对 HL60 的 IC50 为 30 μ g/ml ，小分子肽对白血病细胞和 SCG7901 的抑制率明显高于 PSP 和 PSK 组，在增加白细胞数和 IgG 水平上亦具有增强免疫的效果。于接种前 2 星期使用，可减轻接种癌细胞裸鼠瘤块的发生。 PSk 作为化学预防剂，可作用于肿瘤细胞的生长过程，加强 T 细胞和自然杀伤（NK）细胞的作用，有抗畸变，预防染色体损伤和免疫调节作用。

  1. Ho JC, et al., Fungal polysaccharopeptide inhits tumor angiogenesis and tumor growth in mice. Life Sci. 2004 July.
  2. Song LC, et al., Effects of Coriolus versicolor polysaccharide B on monocyte chemoattractant protein 1 gene expression in rat . Acta Pharmacol Sin. 2002 June.
  3. Qian ZM, et al., Polysaccharide peptide (PSP) restores immunosuppression induced by cyclophosphamide in rats. Am J Chin Med. 1997.
  4. Dong Y, et al., Antitumor effects of a refined polysaccharide peptide fraction isolated from Coriolus versicolor: in vitro and in vivo studies. Res Commun Mol Pathol Pharmacol. 1996 May.
  5. Fujii T, et al., Prolongation of the survival period with the biological response modifier PSK in rats bearing N-methyl-N-nitrosourea-induced mammary gland tumors. In Vivo. 1995 Jan-Feb.
  6. Kanoh T, et al., Enhancement of the antitumor effect by the concurrent use of a monoclonal antibody and the protein-bound polysaccharide PSK in mice bearing a human cancer cell line. In Vivo. 1994 Mar-Apr.
  7. Kanoh T, et al., Suppression of in vivo tumor-induced angiogenesis by the protein-bound polysaccharide PSK. In Vivo. 1994 Mar-Apr.
  8. Matsunaga K, et al., Enhancement of effector cell activities in mice bearing syngeneic plasmacytoma X5563 by a biological response modifier, PSK. J Clin Lab Immunol. 1992 Jan.
  9. Nakajima T, et al., Effects of a protein-bound polysaccharide from a basidiomycetes against hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene in rats. Clin Ther. 1990 Sep-Oct.
  10. Ebina T, et al., Antitumor effect of PSK: role of regional lymph nodes and enhancement of concomitant and sinecomitant immunity in the mouse. Jpn J Cancer Res. 1989 Feb.
  11. Fujita H, et al., Effect of PSK, a protein-bound polysaccharide from Coriolus versicolor, on drug-metabolizing enzymes in sarcoma-180 bearing and normal mice. Int J Immunopharmacol. 1988.
  12. Mastsunaga K, et al., Restoration of immune responsiveness by a biological response modifier, PSK, in aged mice bearing syngeneic transplantable tumor. J Clin Lab Immunol. 1987 Nov.
  13. Fujii T, et al., Effect of PSK on prohibited immunity of splenectomized mice. Anticancer Res. 1987 Jul-Aug.
  14. Mori H, et al., Effect of immunostimulants and antitumor agents on tumor necrosis factor (TNF) production. Int J Immunopharmacol. 1987.
  15. Matsunaga K,et al., [Restoration of immunologic responsiveness by PSK in tumor-bearing animals]. Gan To Kagaku Ryoho. 1986 Dec.
  16. Matsunaga K, et al., [Restoration of depressed immune responses by PSK in C3H/He mice bearing the syngeneic X5563 tumor] Gan To Kagaku Ryoho. 1986 Dec.
  17. Miyaji C, et al., Combination therapy of radiation and immunomodulators in the treatment of MM46 tumor transplanted in C3H/He mice. Oncology. 1983.
  18. Hattori T, et al., Survival time of tumor-bearing rats as related to operative stress and immunopotentiators. Jpn J Surg. 1982.

CLINICAL:

PSK and PAP effects upon the immune system were evaluated by randomized trials and three prospective controlled studies. The RCT for colon and gastric patients found positive effects on immune function influenced by the duration but not the frequency of administration. The first prospective study for head and neck cancer had mixed results: PSK reduced the immune inhibition by radiation but had no effect on the transformation of lymphocytes. The second study of gastric cancer patients and healthy volunteers found that tumor necrosis factor alpha and interleukin-8 gene expression were significantly induced in five of volunteers and four of nine cancer patients. The third prospective controlled trial reported that PSK reduced the decline in leukocytes and platelets associated with chemotherapy, but not as much as another immune stimulator, Granulocyte Colony Stimulating Factor (G-CSF). PSK and G-CSF combined were associated with actual recovery of these blood counts; however, measures of statistical significance were not reported.

Two clinic series studies examined other potential effects of PSK in patients with gastric cancer. One series reported that PSK showed antioxidant activity in serum and serum-free systems. The other series reported that PSK did not interfere with the metabolism of 5-FU chemotherapy.

All trials of PSK have been in combination or supplemental to chemotherapy and/or radiation. These trials have included numerous randomized, but non-blinded, clinical trials in Japan where it has been approved as an adjuvant (supplementary) treatment for digestive system, lung, and nasopharyngeal cancers 10 . PSP has had fewer trials, all of them in China.

  1. Alliot C, Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer. Br J Cancer. 2004 Aug 10.
  2. Ohwada S, et al., Reply: Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer. Br J Cancer. 2004 Aug 10.
  3. Ohwada S, et al., Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study. Br J Cancer. 2004 Mar 8.
  4. Ito K, et al., Long-term effect of 5-fluorouracil enhanced by intermittent administration of polysaccharide K after curative resection of colon cancer. A randomized controlled trial for 7-year follow-up. Int J Colorectal Dis. 2004 Mar.
  5. Ohwada S, et al., Adjuvant therapy with protein-bound polysaccharide K and tegafur uracil in patients with stage II or III colorectal cancer: randomized, controlled trial. Dis Colon Rectum. 2003 Aug.
  6. Fisher M, et al., Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy. Anticancer Res. 2002 May-Jun.
  7. Shibata M, et al., Immunomodulatory effects of low dose cis -Diaminedichloroplatinum (cisplatin) combined with UFT and PSK in patients with advanced colorectal cancer. Cancer Investigation. 2002; 20(2):166-73.
  8. Munemoto Y, et al., Significance of postoperative adjuvant immunochemotherapy after curative resection of colorectal cancers: Association between host or tumor factors and survival. International Journal of Oncology. 2002 Feb; 20(2): 403-11.
  9. Toge T, et al., Protein-bound polysaccharide increases survival in resected gastric cancer cases stratified with a preoperative granulocyte and lymphocyte count. Oncology Reports. 2000 Sep-2000 Oct; 7(5):1157-61.
  10. Saji S, et al., Impact of splenectomy and immunochemotherapy on survival following gastrectomy for carcinoma: covariate interaction with immunosuppressive acidic protein, a serum marker for the host immune system. Tumor Marker Committee for the Study Group of Immunochemotherapy with PSK for Gastric Cancer. Surgery Today. 1999; 29(6): 504-10.
  11. Ogoshi K, et al., Immunotherapy and combined assay of serum levels of carcinoembryonic antigen and acute-phase reactants. Cancer Immunology, Immunotherapy. 1998 Mar; 46(1): 14-20.
  12. Ogoshi K, etb al., HLA-A2 antigen status predicts metastasis and response to immunotherapy in gastric cancer. Cancer Immunology , Immunotherapy. 1997 Oct; 45(1): 53-9.
  13. Katoh R, et al., Changes in serum soluble IL-2 receptors (sIL-2R) and immunosuppressive acidic protein (IAP) associated with chemotherapy for lung cancer. Anticancer Research. 1997 Sep-1997 Oct; 17(5B):3787-92.
  14. Sugimachi K, et al., Dose intensity of uracil and tegafur in postoperative chemotherapy for patients with poorly differentiated gastric cancer. Cancer Chemotherapy & Pharmacology 1997 Jul; 40(3):233-8.
  15. Mao XW, et al., Immunotherapy with low-dose interleukin-2 and a polysaccharopeptide derived from Coriolus versicolor. Cancer Biother Radiopharm. 1996 Dec.
  16. Ogoshi K, et al., Immunotherapy for esophageal cancer: A randomized trial in combination with radiotherapy and radiochemotherapy. American Journal of Clinical Oncology 1995; 18(3):216-22.
  17. Ogoshi K, et al., Possible predictive markers of immunotherapy in esophageal cancer: Retrospective analysis of a randomized study. Cancer Investigation 1995; 13(4):363-9.
  18. Iino Y, et al., Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Anticancer Research 1995; 15:2907-12.
  19. Kato M, et al., Induction of gene expression for immunomodulating cytokines in peripheral blood mononuclear cells in response to orally administered PSK, an immunomodulating protein-bound polysaccharide. Cancer Immunology, Immunotherapy 1995; 40:152-6.
  20. Nakazato H, et al., Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. The Lancet 1994; 343:1122-6.
  21. Hayakawa K, et al., Effect of Krestin (PSK) as adjuvant treatment on the prognosis after radical radiotherapy in patients with non-small cell lung cancer. Anticancer Research 1993; 13:1815-20.
  22. Maehara Y, et al., Postoperative PSK and OK-432 immunochemotherapy for patients with gastric cancer. Cancer Chemotherapy & Pharmacology 1993; 33(2): 171-5.
  23. Mitomi T, et al., Randomized, controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. Diseases of the Colon and Rectum 1992; 35(2):123-30.
  24. Toi M, et al., Randomized adjuvant trial to evaluate the addition of Tamoxifen and PSK to chemotherapy in patients with primary breast cancer. Five-year results from the Nishi-Nippon Group of the Adjuvant Chemoendocrine Therapy for Breast Cancer Organization. Cancer 1992;70(10):2475-83.
  25. Nio Y, et al. Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer. Biotherapy 1992; 4:117-28.
  26. Kariya K, et al., Mimicking of superoxide dismutase activity by protein-bound polysaccharide of Coriolus versicolor QUEL, and oxidative stress relief for cancer patients. Molecular Biotherapy 1992 Mar; 4(1):40-6.
  27. Anai H, et al., A protein-bound polysaccharide immunomodulator, PSK, does not suppress the conversion from 1-(2-tetrahydrofuryl)-5-fluorouracil to 5-fluorouracil in patients with gastric cancer. Anti-Cancer Drugs 1991 Jun; 2(3):275-8.
  28. Kawa K, et al., Effects of biological response modifiers on childhood ALL being in remission after chemotherapy. Biomedicine & Pharmacotherapy 1991; 45: 113-6.
  29. Torisu M, et al., Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer. Cancer Immunology, Immunotherapy 1990; 31:261-8.
  30. Go P, et al., Adjuvant PSK immunotherapy in patients with carcinoma of the nasopharynx. The Journal of International Medical Research 1989; 17:141-9.
  31. Niimoto M, et al., Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years. Japanese Journal of Surgery 1988; 18(6):681-6.
  32. Chung C-H, et al., PSK immunotherapy in cancer patients - a preliminary report. Chinese Journal of Microbiology and Immunology 1987; 20:210-6.
  33. Ohno R, et al., A randomized trial of chemoimmunotherapy of acute nonlymphocytic leukemia in adults using a protein-bound polysaccharide preparation. Cancer Immunology, Immunotherapy 1984;18:149-54.
  34. Kano T, et al., Late results of postoperative long-term cancer chemotherapy for the gastric cancer patients subjected to curative resection. Japanese Journal of Surgery 1983; 13 (2):112-6.
  35. Kodama Y, et al., Combined effect of prophylactic lymphadenectomy and long term combination chemotherapy for curatively resected carcinoma of the stomach. Japanese Journal of Surgery 1982; 12(4): 244-8.
  36. Kano T, et al., Postoperative long-term cancer chemotherapy (PLCC) extends life-span of non-curatively resected patients with stage IV gastric cancer. Japanese Journal of Surgery 1982; 12(3):201-7.
  37. Kano T, et al., Late results of postoperative long term cancer chemotherapy for advanced carcinoma of the stomach. Japanese Journal of Surgery 1981; 11(4):291-6.
  38. Nagao T, et al., Chemoimmunotherapy with Krestin in acute leukemia. Tokai Journal of Experimental & Clinical Medicine 1981;6(2):141-6.
  39. Takahashi H, et al., Clinical experience of PSK to head and neck cancer; with special reference to combination with irradiation. Gan Kagakuryoho 1980; 7(3): 489-95.

 

Safety

No serious risks are associated with the use of PSK and PSP. Side effects that occur infrequently include nausea, vomiting, and diarrhea. Even less common are rash, anorexia, anemia, liver dysfunction, and darkening of the fingernails, but these effects have been limited and general safety has been demonstrated with daily oral doses for extended periods of time. It does not seem to interact with hepatic drug-metabolizing enzymes involved in the chemical processing of most chemotherapy agents, and no genetic damage has been detected by the Ames test.

Although side effects are uncommon, some patients have reported stomach or intestinal upset. No genetic damage has been reported from the Ames test.

There are no known risks associated with Coriolus versicolor use; however, no one should attempt to identify this mushroom on their own because of the danger of choosing a poisonous variety.

毒性及不良反应：云芝多糖肽（PSP）小鼠腹腔半数致死量为 300.36mg/kg，口服最大耐受量为 20g/kg，尚未见小鼠死亡，说明其最小致死量 MLD ＞ 20g/kg。大鼠口服 PSK1.5g/kg (为临床剂量的 130 倍), 连续 60 天， 20 只大鼠无一死亡，表明口服用药无长期毒性反应。实验表明 PSK 为一毒性很低的物质，也无致突变作用。

 

　

 
   
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